Wild-type levels of pregenomic RNA and replication but reduced pre-C RNA and e-antigen synthesis of hepatitis B virus with C(1653) --> T, A(1762) --> T and G(1764) --> A mutations in the core promoter.
Hepatitis B virus (HBV) isolates with A-1762 to T and G-1764 to A mutations in the core promoter have been associated with active hepatitis, severe liver disease following liver transplantation, hepatocellular carcinoma and acute fulminant courses--in the latter case combined with a C-1653 to T mutation. In this study, a mutant core promoter region containing the T-1653, T-1762 and A-1764 mutations was placed into the context of a wild-type HBV genome and analysed by transfection. The mutations reduced the level of pre-C mRNA (by 55%) and e-antigen secretion. In contrast, no significant effects on the levels of pregenome/C and pre-S/S mRNAs, intracellular core, polymerase, and pre-S /S2 proteins and secreted S-antigen were observed. The amount of progeny virus DNA in the cells and in the culture medium was increased marginally, if at all.
Günther
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S
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Federal Republic of Germany. will@hpi.uni-hamburg.de
Piwon
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N
Will
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H
D001483:Base Sequence; D004279:DNA, Viral / Q000302:isolation & purification; D016679:Genome, Viral; D006509:Hepatitis B / Q000097:blood / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D012322:RNA Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis*; D014779:Virus Replication
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D012322:RNA Precursors; D012333:RNA, Messenger; D012367:RNA, Viral